Skip to content
1887

Abstract

Several inhibitors of ornithine and arginine decarboxylases reduced growth of the fungus cultured on Czapek Dox agar. Of these, the most effective were difluoromethylornithine (DFMO), dehydromonofluoro-methylornithine, difluoromethylarginine and dehydromonofluoromethylarginine. The growth inhibition due to 1 m-DFMO could be partially reversed with 1 μ-putrescine. Other compounds causing significant reversal of DFMO-mediated growth inhibition included diaminopentane (cadaverine), diaminoheptane, spermidine, 7,7-difluorospermidine, spermine, bis(2-aminoethyl)amine, 2-hydroxy-1,3-diaminopropane, monoacetylputrescine, butenediamine and aminoguanidine. Some compounds, which were relatively innocuous by themselves, increased growth inhibition due to DFMO. Notably effective compounds were methylacetylenicputrescine, aminooxyaminopropane, butynediamine, 2,2-difluoroputrescine, diacetylputrescine, methylglyoxal bis(guanylhydrazone), streptomycin, certain methylated amines, and cyclohexylamine and related compounds. Growth inhibition due to a homologous series of diguanidines [NHC(=NH)NH(CH)NHC(=NH)NH] was also tested. These were especially effective when = 12, and when = 5 or 6. In general, the results suggest that amino-acid-based inhibitors of ornithine decarboxylase have a greater permeability than amine-based inhibitors.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-136-6-985
1990-06-01
2025-04-18
Loading full text...

Full text loading...

/deliver/fulltext/micro/136/6/mic-136-6-985.html?itemId=/content/journal/micro/10.1099/00221287-136-6-985&mimeType=html&fmt=ahah

References

  1. Alhonen-Hongisto L., Seppänen P., Jänne J. 1980; Intracellular putrescine and spermidine deprivation induces increased uptake of the natural polyamines and methylglyoxal bis(guanylhydrazone). Biochemical Journal 192:941–945
    [Google Scholar]
  2. Bachrach U., Heimer Y.M. eds 1988 The Physiology of Polyamines. Boca Raton, Florida:: CRC Press.;
    [Google Scholar]
  3. Bey P., Danzin C., Jung M. 1987; Inhibition of basic amino acid decarboxylases involved in polyamine biosynthesis. In Inhibition of Polyamine Metabolism pp. 1–31 Mccann P. P., Pegg A. E., Sjoerdsma A. Edited by Orlando: Academic Press;
    [Google Scholar]
  4. Bitonti A.J., Mccann P.P. 1987; Inhibition of polyamine biosynthesis in microorganisms. In Inhibition of Polyamine Metabolism pp. 259–275 Mccann P. P., Pegg A. E., Sjoerdsma A. Edited by Orlando: Academic Press;
    [Google Scholar]
  5. Bitonti A.J., Dumont J.A., Mccann P.P. 1986; Characterization of Trypanosoma brucei brucei S-adenosyl-l-methionine decarboxylase and its inhibition by Berenil, pentamidine and methyl-glyoxal bis(guanylhydrazone). Biochemical Journal 237:685–689
    [Google Scholar]
  6. Bitonti A.J., Bush T.L., Mccann P.P. 1989a; Regulation of polyamine biosynthesis in rat hepatoma (HTC) cells by a fcbenzyl polyamine analogue. Biochemical Journal 257:769–774
    [Google Scholar]
  7. Bitonti A.J., Dumont J.A., Bush T.L., Edwards M.L., Stemerick D.M., Mccann P.P., Sjoerdsma A. 1989b; Bis(benzyl)polyamine analogs inhibit the growth of chloroquine-resistant human malaria parasites (Plasmodium falciparum) in vitro, and in combination with α-difluoromethylomithine cure murine malaria. Proceedings of the National Academy of Sciences of the United States of America 86:651–655
    [Google Scholar]
  8. Boyle S.M., Sriranganathan N., Cordes D. 1988; Susceptibility of Microsporum and Trichophyton species to suicide inhibitors of polyamine biosynthesis. Journal of Medical and Veterinary Mycology 26:227–235
    [Google Scholar]
  9. Brown D., Woodcock D. 1973; Fungicidal activity and chemical constitution. XXI. The fungitoxicity of aliphatic polyamines. Pesticide Science 4:485–490
    [Google Scholar]
  10. Carson C.M., Mccann P.P. 1988; Method of controlling phytopathogenic fungus. US Patent 4760091 Chemical Abstracts 109: 185468
    [Google Scholar]
  11. Casero R.A., Ervin S.J., Celano P., Bayun S.B., Bergeron R.J. 1989; Differential response to treatment with the bis(ethyl)-polyamine analogues between human small cell lung carcinoma and undifferentiated large cell lung carcinoma in culture. Cancer Research 49:639–643
    [Google Scholar]
  12. Davidse L.C. 1984; Antifungal activity of acylalanine fungicides and related chloroacetanilide herbicides. In Mode of Action of Antifungal Agents pp. 239–255 Trinci A. P. J., Ryley J. F. Edited by Cambridge: Cambridge University Press;
    [Google Scholar]
  13. Davis R.H., Ristow J.L. 1989; Uptake, intracellular binding and excretion of polyamines during growth of Neurospora crassa. Archives of Biochemistry and Biophysics 271:315–322
    [Google Scholar]
  14. Dekker J. 1984; Development of resistance to antifungal agents. In Mode of Action of Antifungal Agents pp. 89–111 Trinci A. P. J., Ryley J. F. Edited by Cambridge: Cambridge University Press;
    [Google Scholar]
  15. Elferink J.G.R. 1975; Influence of spermine on some membrane-disturbing actions. Zeitschrift für Naturforschung 30c:117–119
    [Google Scholar]
  16. Haywood G.W., Large P.J. 1986; 4-Acetamidobutyrate deacetylase in the yeast Candida boidinii grown on putrescine or spermidine as sole nitrogen source and its probable role in polyamine catabolism. Journal of General Microbiology 132:7–14
    [Google Scholar]
  17. Hudson H.R., Ojo I.A.O., Pianka M. 1986; Guanidines with antifungal (and antibacterial) activity - a review. International Pest Control pp. 148–155
    [Google Scholar]
  18. Hyvonen T., Alakuijala L., Andersson L., Khomutov A.R., Khomutov R.M., Eloranta T.O. 1988; 1-Aminooxy-3-aminopropane reversibly prevents the proliferation of cultured baby hamster kidney cells by interfering with polyamine synthesis. Journal of Biological Chemistry 263:11138–11144
    [Google Scholar]
  19. Khan A.J., Minocha S.C. 1989; Biosynthetic arginine decarboxylase in phytopathogenic fungi. Life Sciences 44:1215–1222
    [Google Scholar]
  20. Massart L. 1948; Antagonism between basic compounds (spermine, streptomycin) and basic bactericidal substances. Nature; London: 162779
    [Google Scholar]
  21. Nagarajan S., Ganem B., Pegg A.E. 1988; Studies of non-metabolizable polyamines that support growth of SV-3T3 cells depleted of natural polyamines by exposure to α-difluoromethyl-ornithine. Biochemical Journal 254:373–378
    [Google Scholar]
  22. Pfaller M.A., Riley J., Gerarden T. 1988; Polyamine depletion and growth inhibition in Candida albicans and Candida tropicalis by α-difluoromethylornithine and cyclohexylamine. Journal of Medical and Veterinary Mycology 26:119–126
    [Google Scholar]
  23. Porta R., Camardella M., Desantis A., Gentile V., Sellinger O.Z. 1983; Polyamines and methionine sulfoximine-induced seizures. Advances in Polyamine Research 4:209–219
    [Google Scholar]
  24. Porter C.W., Bergeron R.J. 1988; Enzyme regulation as an approach to interference with polyamine biosynthesis - an alterna-tive to enzyme inhibition. Advances in Enzyme Regulation 27:57–79
    [Google Scholar]
  25. Rajam M.V., Galston A.W. 1985; The effects of some polyamine biosynthetic inhibitors on growth and morphology of phytopathogenic fungi. Plant and Cell Physiology 26:683–692
    [Google Scholar]
  26. Rajam M.V., Weinstein L.H., Galston A.W. 1989; Inhibition of uredospore germination and germ tube growth by inhibitors of polyamine metabolism in Uromyces phaseoli L. Plant and Cell Physiology 30:37–41
    [Google Scholar]
  27. Sarhan S., Dezeure F., Seiler N. 1987; Putrescine derivatives as substrates of spermidine synthase. International Journal of Biochemistry 19:1037–1047
    [Google Scholar]
  28. Seiler N., Knödgen B., Bink G., Sarhan S., Bolkenius F. 1983; Diamine oxidase and polyamine catabolism. Advances in Polyamine Research 4:135–154
    [Google Scholar]
  29. Shapira R., Altman A., Henis Y., Chet I. 1989; Polyamines and ornithine decarboxylase activity during growth and differentiation in Sclerotium rolfsii. Journal of General Microbiology 135:1361–1367
    [Google Scholar]
  30. Shirahata A., Morohoshi T., Samejima K. 1988; Trans-4-methylcyclohexylamine, a potent new inhibitor of spermidine synthase. Chemical and Pharmaceutical Bulletin 36:3220–3222
    [Google Scholar]
  31. Smith T.A., Marshall J.H.A. 1988; The oxidative decarboxylation of ornithine by extracts of higher plants. Phytochemistry 27:703–710
    [Google Scholar]
  32. Smith T.A., Barker J.H.A., Jung M. 1990; Effect of enzyme-activated inhibitors on ornithine decarboxylase and growth of Botrytis cinerea. Phytochemistry 29: (in the Press)
    [Google Scholar]
  33. Stevens L., Mckinnon I.M. 1977; The effect of 1,4-diaminobutanone on the stability of ornithine decarboxylase from Aspergillus nidulans. Biochemical Journal 166:635–637
    [Google Scholar]
  34. Tabor H., Tabor C.W., Demeis L. 1971; Chemical synthesis of N-acetyl-l-4-diaminobutane, N1 -acetylspermidine, and N8-acetyl-spermidine. Methods in Enzymology 17B:829–833
    [Google Scholar]
  35. Tan K.K., Epton H.A.S. 1973; Effect of light on the growth and sporulation of Botrytis cinerea. Transactions of the British Mycological Society 61:147–157
    [Google Scholar]
  36. Trione E.J., Stockwell V.O., Austin H.A. 1988; The effects of polyamines on the growth and development of the wheat bunt fungi. Botanical Gazette 149:173–178
    [Google Scholar]
  37. Tyms A.S., Williamson J.D., Bacchi C.J. 1988; Polyamine inhibitors in antimicrobial chemotherapy. Journal of Antimicrobial Chemotherapy 22:403–427
    [Google Scholar]
  38. Weinstein L.H., Galston A.W. 1988; Prevention of a plant disease by specific inhibition of fungal polyamine biosynthesis. International Publication no. WO 88/02986. Chemical Abstracts 109: 106 548
    [Google Scholar]
  39. Walters D. 1989; Polyamines and plant disease. Plants TodayJan-Feb 198922–26
    [Google Scholar]
/content/journal/micro/10.1099/00221287-136-6-985
Loading
/content/journal/micro/10.1099/00221287-136-6-985
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error